INTRAVENTRICULAR GLP-1 REDUCES SHORT-TERM BUT NOT LONG-TERM FOOD-INTAKE OR BODY-WEIGHT IN LEAN AND OBESE RATS

Glucagon-like-peptide-1 (7-36) amide (GLP-1), when infused into the th ird ventricle (IVT), reduces short-term food intake. In the present ex periments, we assessed whether NT administration of GLP-1 could influe nce long-term food intake and body weight of lean Long Evans rats and of fatty Zucker (fa/fa) rats. In Experiment 1, we replicated the obser vation that 10 mu g GLP-1, given IVT, reduces one and 2 h food intake, and extended the observation to fatty Zucker rats. However, in both r at strains, 24 h food intake and body weight were unchanged by this ac ute treatment. In Experiment 2, GLP-1 (30 mu g/day) was infused IVT co ntinuously for 4 days via an osmotic mini-pump. This treatment also ha d no effect on food intake or body weight in either Long-Evans or fatt y Zucker rats. A control experiment verified that the GLP-1 remained b iologically active over the duration of the infusion period. In a fina l experiment, Long-Evans rats were restricted to two 2 h periods of ac cess to food each day for 6 days. Prior to each of these access period s, rats received either 15 mu g of GLP-1 IVT or a vehicle control inje ction. While GLP-1 significantly reduced food intake on the first day of treatment, this effect of GLP-1 rapidly disappeared such that it wa s reduced on the second day and absent on the third day; and there was no effect on body weight at any time. Collectively, the present exper iments do not support the hypothesis that GLP-1, acting in the CNS, is an important regulator of long-term food intake and body weight. (C) 1998 Elsevier Science B.V.